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Article first published online: 11 FEB 2005
© 2005 Wiley-Liss, Inc.
Volume 25, Issue 3, pages 248–258, March 2005
How to Cite
Nishiguchi, K. M., Sandberg, M. A., Gorji, N., Berson, E. L. and Dryja, T. P. (2005), Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum. Mutat., 25: 248–258. doi: 10.1002/humu.20142
Communicated by Peter Humphries
The Supplementary Material referred to in this article can be accessed at http://www.interscience.wiley.com/jpages/1059-7794/suppmat.
- Issue published online: 23 FEB 2005
- Article first published online: 11 FEB 2005
- Manuscript Accepted: 15 SEP 2004
- Manuscript Received: 18 JUN 2004
- Foundation Fighting Blindness, Owings Mills, MD
- National Eye Institute. Grant Numbers: EY08683, EY00169
- color blindness;
- macular degeneration;
Unrelated patients with achromatopsia, macular degeneration with onset under age 50 years, cone degeneration or dysfunction, cone-rod degeneration, or macular malfunction were screened for mutations in the three genes known to be associated with achromatopsia: the GNAT2 gene encoding the α subunit of cone transducin and the CNGA3 and CNGB3 genes encoding the α and β subunits of the cone cGMP-gated cation channel. We found no examples of patients with GNAT2 mutations. Out of 36 achromats, 12 (33%) had mutations in CNGA3 (13 different mutations including five novel mutations) and 12 (33%) had mutations in CNGB3 (six different mutations including four novel mutations). All achromats with CNG mutations had residual, presumably cone function as determined by computer-averaged 30-Hz electroretinograms (ERGs). There was considerable variability in acuity and color vision, with most patients having acuities of 20/200–20/400 and complete absence of color perception, and others having acuities of 20/25–20/40 and some color vision. Two pseudodominant achromatopsia cases were uncovered, both with CNGA3 mutations, including one family in which some compound heterozygotes with achromatopsia mutations were clinically unaffected. We found two novel CNGB3 changes in three patients with juvenile macular degeneration, a phenotype not previously associated with mutations in the cone channel subunits. These patients had subnormal acuity (20/30–20/60), normal to subnormal color vision, and normal to subnormal full-field cone ERG amplitudes. Our results indicate that some patients with channel protein mutations retain residual foveal cone function. Based on our findings, CNGB3 should be considered as a candidate gene to be evaluated in patients with forms of cone dysfunction, including macular degeneration. Hum Mutat 25:248–258, 2005. © 2005 Wiley-Liss, Inc.